(E)-3-(furan-2-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-3-(furan-2-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 英文别名: (E)-3-(2-furyl)-1-(2-hydroxy-4-methoxy-phenyl)prop-2-en-1-one
• 化学式: C₁₄H₁₂O₄
• 分子量: 244.247
• InChiKey: HYFUNIRTCZNDOT-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  59.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(furan-2-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one 在 双氧水 、 三溴化硼 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 48.0h， 生成 2-(furan-2-yl)-3,7-dihydroxy-4H-chromen-4-one
  参考文献：
  名称：

  Discovery of a benzothiophene-flavonol halting miltefosine and antimonial drug resistance in Leishmania parasites through the application of medicinal chemistry, screening and genomics

  摘要：

  Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain. Compound 19, 2-(benzo[b]thiophen-3-yl)3-hydroxy-6-methoxy-4H-chromen-4-one, exhibited a broad-spectrum activity against Leishmania spp. (EC50 1.9 mu M for Leishmania infantum, 3.4 mu M 4 for L. donovani, 6.7 mu M for L. major), Trypanosoma cruzi (EC50 7.5 mu M) and T. brucei (EC50 0.8 mu M). Focusing on anti-Leishmania activity, compound 19 challenge in vitro did not select for resistance markers in L donovani, while a Cos-Seq screening for dominant resistance genes identified a gene locus on chromosome 36 that became ineffective at concentrations beyond EC50 Thus, compound 19 is a promising scaffold to tackle drug resistance in Leishmania infection. In vivo pharmacokinetic studies indicated that compound 19 has a long half-life (intravenous (IV): 63.2 h; per os (PO): 46.9 h) with an acceptable ADME-Toxicity profile. When tested in Leishmania infected hamsters, no toxicity and limited efficacy were observed. Low solubility and degradation were investigated spectroscopically as possible causes for the sub-optimal pharmacokinetic properties. Compound 19 resulted a specific compound based on the screening against a protein set, following the intrinsic fluorescence changes. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111676
• 作为产物：
  描述：

  糠醛 、 丹皮酚 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以65%的产率得到(E)-3-(furan-2-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Discovery of a benzothiophene-flavonol halting miltefosine and antimonial drug resistance in Leishmania parasites through the application of medicinal chemistry, screening and genomics

  摘要：

  Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain. Compound 19, 2-(benzo[b]thiophen-3-yl)3-hydroxy-6-methoxy-4H-chromen-4-one, exhibited a broad-spectrum activity against Leishmania spp. (EC50 1.9 mu M for Leishmania infantum, 3.4 mu M 4 for L. donovani, 6.7 mu M for L. major), Trypanosoma cruzi (EC50 7.5 mu M) and T. brucei (EC50 0.8 mu M). Focusing on anti-Leishmania activity, compound 19 challenge in vitro did not select for resistance markers in L donovani, while a Cos-Seq screening for dominant resistance genes identified a gene locus on chromosome 36 that became ineffective at concentrations beyond EC50 Thus, compound 19 is a promising scaffold to tackle drug resistance in Leishmania infection. In vivo pharmacokinetic studies indicated that compound 19 has a long half-life (intravenous (IV): 63.2 h; per os (PO): 46.9 h) with an acceptable ADME-Toxicity profile. When tested in Leishmania infected hamsters, no toxicity and limited efficacy were observed. Low solubility and degradation were investigated spectroscopically as possible causes for the sub-optimal pharmacokinetic properties. Compound 19 resulted a specific compound based on the screening against a protein set, following the intrinsic fluorescence changes. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111676

文献信息

• [EN] PROSTAGLANDIN REDUCTASE INHIBITORS<br/>[FR] INHIBITEURS DE PROSTAGLANDINE RÉDUCTASES
  申请人：ABGENOMICS CORP

  公开号：WO2007082178A2

  公开（公告）日：2007-07-19

  [EN] A method of inhibiting 15-keto prostaglandin-?¹³-reductase 2 by contacting 15-keto prostaglandin-?¹³-reductase 2 with an aryl compound of Formula (I), (II), (III), or (IV) shown herein. Also disclosed are methods of treating peroxisome proliferators-activated receptor related diseases and lowering blood glucose levels by administering to a subject in need thereof an effective amount of such an aryl compound.
  [FR] Procédé d'inhibition de la 15-céto-prostaglandine-?¹³-réductase 2 par la mise en contact de la 15-céto-prostaglandine-?¹³-réductase 2 avec un composé aryle de formule (I), (II), (III) ou (IV) illustrée dans la présente invention. La présente invention concerne également des procédés de traitement de maladies liées au récepteur activé par des proliférateurs de peroxysome et d'abaissement des taux de glucose sanguin en administrant une quantité efficace de ce composé d'aryle à un sujet nécessitant un tel traitement.